@article{8f6181eeaee843f4b9a893eedd590f24,
title = "Long-term diazepam treatment enhances microglial spine engulfment and impairs cognitive performance via the mitochondrial 18 kDa translocator protein (TSPO)",
abstract = "Benzodiazepines are widely administered drugs to treat anxiety and insomnia. In addition to tolerance development and abuse liability, their chronic use may cause cognitive impairment and increase the risk for dementia. However, the mechanism by which benzodiazepines might contribute to persistent cognitive decline remains unknown. Here we report that diazepam, a widely prescribed benzodiazepine, impairs the structural plasticity of dendritic spines, causing cognitive impairment in mice. Diazepam induces these deficits via the mitochondrial 18 kDa translocator protein (TSPO), rather than classical γ-aminobutyric acid type A receptors, which alters microglial morphology, and phagocytosis of synaptic material. Collectively, our findings demonstrate a mechanism by which TSPO ligands alter synaptic plasticity and, as a consequence, cause cognitive impairment.",
author = "Yuan Shi and Mochen Cui and Katharina Ochs and Matthias Brendel and Str{\"u}bing, {Felix L.} and Nils Briel and Florian Eckenweber and Chengyu Zou and Banati, {Richard B.} and Liu, {Guo Jun} and Middleton, {Ryan J.} and Rainer Rupprecht and Uwe Rudolph and Zeilhofer, {Hanns Ulrich} and Gerhard Rammes and Jochen Herms and Dorostkar, {Mario M.}",
note = "Funding Information: We would like to thank G. Mitteregger, M. Miller, A. von Thaden, M. Schneider, C. Ihbe, E. G{\"o}cmenoglu, N. Lachner, F. Zhang, M. Matt and R. Trevisi for their technical support and animal care. We also thank A. Giese for support in discussing and preparing this manuscript. The DZNE Brain Bank provided advice on human tissue use. We appreciate the help of S. Reinert and T. Bonhoeffer in establishing in vivo imaging using microprism. We are grateful to B. von Ungern-Sternberg and K. Bormann-Giglmaier for technical assistance in PET scanning. The authors thank Plexxikon Inc. for providing PLX5622. This work was funded by Deutsche Forschungsgemeinschaft grants (FOR 2858 / ID 422181340 to J.H. and M.M.D., ID 420462116 to R.R. and EXC 2145 / ID 390857198 to J.H.). Funding Information: We would like to thank G. Mitteregger, M. Miller, A. von Thaden, M. Schneider, C. Ihbe, E. G{\"o}cmenoglu, N. Lachner, F. Zhang, M. Matt and R. Trevisi for their technical support and animal care. We also thank A. Giese for support in discussing and preparing this manuscript. The DZNE Brain Bank provided advice on human tissue use. We appreciate the help of S. Reinert and T. Bonhoeffer in establishing in vivo imaging using microprism. We are grateful to B. von Ungern-Sternberg and K. Bormann-Giglmaier for technical assistance in PET scanning. The authors thank Plexxikon Inc. for providing PLX5622. This work was funded by Deutsche Forschungsgemeinschaft grants (FOR 2858 / ID 422181340 to J.H. and M.M.D., ID 420462116 to R.R. and EXC 2145 / ID 390857198 to J.H.). Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2022",
month = mar,
doi = "10.1038/s41593-022-01013-9",
language = "English (US)",
volume = "25",
pages = "317--329",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "3",
}